(1) Field of the Invention
The present invention relates to novel antibiotic erythromycin derivatives, and more particularly relates to novel 6-0-methylerythromycin A 9-oxime derivatives and the salts thereof having strong antibacterial activity against erythromycin resistant bacteria.
(2) Prior Art
Erythromycin A is an antibiotic which is widely clinically used as a therapeutical agent for treatment of infectious diseases caused by many Gram-positive bacteria, a certain Gram-negative bacteria and mycoplasma. The main disadvantage of erythromycin A is low acid-stability which leads to low and inconsistent oral absorption. Among Gram-positive bacteria are known bacteria which have lower sensitivity to erythromycin A than to the other pathogenic bacteria and are resistant to erythromycin A. In order to improve such biological and pharmacodynamical properties of erythromycin A, many derivatives have been prepared. For example, there are disclosed erythromycin 9-oxime ether derivatives in U.S. Pat. No. 4,349,545, 6-0-methylerythromycin derivatives in U.S. Pat. Nos. 4,331,803 and 4,680,386 and E.P. Patent No. 245,013.
The above-mentioned derivatives solved moderately the problem of the low acid-stability which is a disadvantage of erythromycin. Accordingly, these derivatives are known to show more excellent in vivo antibacterial activity than erythromycin when administered orally. However, the problem of resistant bacteria against erythromycin A has not yet been sufficiently solved.
E.P. Patent No. 194,833 discloses a series of 6-0-methylerythromycin 9-oxime ether derivatives. However, this patent discloses only a methyl ether derivative in the working example and does not report any activity against erythromycin resistant bacteria.
The present inventors have found that some 6-0-methylerythromycin A 9-oxime derivatives have strong antibacterial activity against erythromycin resistant bacteria.